ArticleCells2025
Inhibition of Tumor Microenvironment-Driven JAK-STAT Signaling Enhances Response to Arginine Deprivation Therapy in Triple-Negative Breast Cancer.
Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed.
- Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy.Natural products and bioprospecting · 2026Review
- JAK-STAT signaling pathway in cancer: from molecular mechanisms to clinical intervention.Molecular cancer · 2026Review
- Breast Cancer Milieu Maneuvers Cancer-Associated Macrophages to Synergize Neoplastic Repertoires.Cancers · 2026Review
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.Oncology research · 2026Review
Corrections and comments
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Authors and funding
29 authors.
Funding
Abstract
Argininosuccinate synthetase 1 (ASS1) expression and arginine availability are key metabolic determinants that influence tumor fitness and regulate immune interactions within the tumor microenvironment (TME). Using an orthotopic triple-negative breast cancer (TNBC) model, we demonstrate that arginine deprivation heightens tumor dependence on the TME for survival. Mechanistically, fibroblasts sustain tumor viability by supplying arginine, whereas macrophages cooperate with stromal cues to activate Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling, thereby enhancing tumor survival. Concordantly, a JAK-STAT gene-expression signature correlates with ASS1 levels in human TNBC datasets. Translationally, combined pharmacological inhibition of JAK signaling with arginine deprivation markedly suppresses tumor growth. Together, these findings reveal a TME-driven, targetable stromal-immune circuit that enables tumors to withstand arginine deficiency-induced metabolic stress. Broadly, our work highlights that mapping and strategically inducing metabolic dependencies can reveal actionable compensatory pathways, offering opportunities to improve cancer therapy.
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Registered trials
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